Association of Ketone Body Levels With Hyperglycemia and Type 2 Diabetes in 9,398 Finnish Men
We investigated the association of the levels of ketone bodies (KBs) with hyperglycemia and with 62 genetic risk variants regulating glucose levels or type 2 diabetes in the population-based Metabolic Syndrome in Men (METSIM) study, including 9,398 Finnish men without diabetes or newly diagnosed typ...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2013-10, Vol.62 (10), p.3618-3626 |
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| creator | MAHENDRAN, Yuvaraj VANGIPURAPU, Jagadish PAJUKANTA, Päivi LUSIS, Aldons J BONNYCASTLE, Lori L MORKEN, Mario A COLLINS, Francis S MOHLKE, Karen L BOEHNKE, Michael ALA-KORPELA, Mika KUUSISTO, Johanna LAAKSO, Markku CEDERBERG, Henna STANCAKOVA, Alena PIHLAJAMÄKI, Jussi SOININEN, Pasi KANGAS, Antti J PAANANEN, Jussi CIVELEK, Mete SALEEM, Niyas K |
| description | We investigated the association of the levels of ketone bodies (KBs) with hyperglycemia and with 62 genetic risk variants regulating glucose levels or type 2 diabetes in the population-based Metabolic Syndrome in Men (METSIM) study, including 9,398 Finnish men without diabetes or newly diagnosed type 2 diabetes. Increasing fasting and 2-h plasma glucose levels were associated with elevated levels of acetoacetate (AcAc) and β-hydroxybutyrate (BHB). AcAc and BHB predicted an increase in the glucose area under the curve in an oral glucose tolerance test, and AcAc predicted the conversion to type 2 diabetes in a 5-year follow-up of the METSIM cohort. Impaired insulin secretion, but not insulin resistance, explained these findings. Of the 62 single nucleotide polymorphisms associated with the risk of type 2 diabetes or hyperglycemia, the glucose-increasing C allele of GCKR significantly associated with elevated levels of fasting BHB levels. Adipose tissue mRNA expression levels of genes involved in ketolysis were significantly associated with insulin sensitivity (Matsuda index). In conclusion, high levels of KBs predicted subsequent worsening of hyperglycemia, and a common variant of GCKR was significantly associated with BHB levels. |
| doi_str_mv | 10.2337/db12-1363 |
| format | Article |
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Increasing fasting and 2-h plasma glucose levels were associated with elevated levels of acetoacetate (AcAc) and β-hydroxybutyrate (BHB). AcAc and BHB predicted an increase in the glucose area under the curve in an oral glucose tolerance test, and AcAc predicted the conversion to type 2 diabetes in a 5-year follow-up of the METSIM cohort. Impaired insulin secretion, but not insulin resistance, explained these findings. Of the 62 single nucleotide polymorphisms associated with the risk of type 2 diabetes or hyperglycemia, the glucose-increasing C allele of GCKR significantly associated with elevated levels of fasting BHB levels. Adipose tissue mRNA expression levels of genes involved in ketolysis were significantly associated with insulin sensitivity (Matsuda index). In conclusion, high levels of KBs predicted subsequent worsening of hyperglycemia, and a common variant of GCKR was significantly associated with BHB levels.</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db12-1363</identifier><identifier>PMID: 23557707</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>Alexandria, VA: American Diabetes Association</publisher><subject>3-Hydroxybutyric Acid - blood ; Acetoacetates - blood ; Area Under Curve ; Biological and medical sciences ; Biomarkers - blood ; Blood Glucose - metabolism ; Care and treatment ; Diabetes ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - epidemiology ; Diabetes Mellitus, Type 2 - genetics ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; European Continental Ancestry Group - genetics ; Fasting ; Finland - epidemiology ; Genetics ; Genome-Wide Association Study ; Glucose metabolism ; Glucose Tolerance Test ; Glucose tolerance tests ; Health aspects ; Humans ; Hyperglycemia ; Hyperglycemia - blood ; Hyperglycemia - epidemiology ; Hyperglycemia - genetics ; Insulin ; Ketone Bodies - blood ; Ketones ; Male ; Medical sciences ; Men ; Metabolic Syndrome - blood ; Metabolic Syndrome - epidemiology ; Middle Aged ; Organic chemicals ; Original Research ; Physiological aspects ; Polymorphism, Single Nucleotide ; Predictive Value of Tests ; Risk Factors ; Type 2 diabetes</subject><ispartof>Diabetes (New York, N.Y.), 2013-10, Vol.62 (10), p.3618-3626</ispartof><rights>2014 INIST-CNRS</rights><rights>COPYRIGHT 2013 American Diabetes Association</rights><rights>COPYRIGHT 2013 American Diabetes Association</rights><rights>Copyright American Diabetes Association Oct 2013</rights><rights>2013 by the American Diabetes Association. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c610t-445281d7948c4ef161fca698a0e55812c8841c698bca42bf8ea69de3a7c102b53</citedby><cites>FETCH-LOGICAL-c610t-445281d7948c4ef161fca698a0e55812c8841c698bca42bf8ea69de3a7c102b53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781437/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781437/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27784746$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23557707$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MAHENDRAN, Yuvaraj</creatorcontrib><creatorcontrib>VANGIPURAPU, Jagadish</creatorcontrib><creatorcontrib>PAJUKANTA, Päivi</creatorcontrib><creatorcontrib>LUSIS, Aldons J</creatorcontrib><creatorcontrib>BONNYCASTLE, Lori L</creatorcontrib><creatorcontrib>MORKEN, Mario A</creatorcontrib><creatorcontrib>COLLINS, Francis S</creatorcontrib><creatorcontrib>MOHLKE, Karen L</creatorcontrib><creatorcontrib>BOEHNKE, Michael</creatorcontrib><creatorcontrib>ALA-KORPELA, Mika</creatorcontrib><creatorcontrib>KUUSISTO, Johanna</creatorcontrib><creatorcontrib>LAAKSO, Markku</creatorcontrib><creatorcontrib>CEDERBERG, Henna</creatorcontrib><creatorcontrib>STANCAKOVA, Alena</creatorcontrib><creatorcontrib>PIHLAJAMÄKI, Jussi</creatorcontrib><creatorcontrib>SOININEN, Pasi</creatorcontrib><creatorcontrib>KANGAS, Antti J</creatorcontrib><creatorcontrib>PAANANEN, Jussi</creatorcontrib><creatorcontrib>CIVELEK, Mete</creatorcontrib><creatorcontrib>SALEEM, Niyas K</creatorcontrib><title>Association of Ketone Body Levels With Hyperglycemia and Type 2 Diabetes in 9,398 Finnish Men</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>We investigated the association of the levels of ketone bodies (KBs) with hyperglycemia and with 62 genetic risk variants regulating glucose levels or type 2 diabetes in the population-based Metabolic Syndrome in Men (METSIM) study, including 9,398 Finnish men without diabetes or newly diagnosed type 2 diabetes. Increasing fasting and 2-h plasma glucose levels were associated with elevated levels of acetoacetate (AcAc) and β-hydroxybutyrate (BHB). AcAc and BHB predicted an increase in the glucose area under the curve in an oral glucose tolerance test, and AcAc predicted the conversion to type 2 diabetes in a 5-year follow-up of the METSIM cohort. Impaired insulin secretion, but not insulin resistance, explained these findings. Of the 62 single nucleotide polymorphisms associated with the risk of type 2 diabetes or hyperglycemia, the glucose-increasing C allele of GCKR significantly associated with elevated levels of fasting BHB levels. Adipose tissue mRNA expression levels of genes involved in ketolysis were significantly associated with insulin sensitivity (Matsuda index). In conclusion, high levels of KBs predicted subsequent worsening of hyperglycemia, and a common variant of GCKR was significantly associated with BHB levels.</description><subject>3-Hydroxybutyric Acid - blood</subject><subject>Acetoacetates - blood</subject><subject>Area Under Curve</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Blood Glucose - metabolism</subject><subject>Care and treatment</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Diabetes Mellitus, Type 2 - epidemiology</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>European Continental Ancestry Group - genetics</subject><subject>Fasting</subject><subject>Finland - epidemiology</subject><subject>Genetics</subject><subject>Genome-Wide Association Study</subject><subject>Glucose metabolism</subject><subject>Glucose Tolerance Test</subject><subject>Glucose tolerance tests</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Hyperglycemia</subject><subject>Hyperglycemia - blood</subject><subject>Hyperglycemia - epidemiology</subject><subject>Hyperglycemia - genetics</subject><subject>Insulin</subject><subject>Ketone Bodies - blood</subject><subject>Ketones</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Men</subject><subject>Metabolic Syndrome - blood</subject><subject>Metabolic Syndrome - epidemiology</subject><subject>Middle Aged</subject><subject>Organic chemicals</subject><subject>Original Research</subject><subject>Physiological aspects</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Predictive Value of Tests</subject><subject>Risk Factors</subject><subject>Type 2 diabetes</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kl9rFDEUxYModm198AtIQPogOG3-zSTzImxX24orfanoi4RM5mY2ZTZZJ7PF_fZmcW1dWOQ-BO795eRychB6RckZ41yetw1lBeUVf4ImtOZ1wZn8_hRNCNn2ZS2P0IuU7gghVa7n6IjxspSSyAn6MU0pWm9GHwOODn-GMQbAF7Hd4DncQ5_wNz8u8PVmBUPXbywsvcEmtPg2dzDDH7xpYISEfcD1O14rfOlD8GmBv0A4Qc-c6RO83J3H6Ovlx9vZdTG_ufo0m84LW1EyFkKUTNFW1kJZAY5W1FlT1coQKEtFmVVKUJsbjTWCNU5BnrbAjbSUsKbkx-j9H93VullCayGMg-n1avBLM2x0NF7vT4Jf6C7eay4VFVxmgTc7gSH-XEMa9V1cDyHvrGnFFKGyLMUj1ZketA8uZjG79MnqKRdCsSpvm6niANVBgPxyNtf53N7jzw7wudrstT144e3ehcyM8GvszDolra7m_1tmx9rY99CBzr8wuzmobYeY0gDuwURK9DZsehs2vQ1bZl__6_oD-TddGTjdASZZ07vBBOvTIyelElJU_DdlBNaf</recordid><startdate>20131001</startdate><enddate>20131001</enddate><creator>MAHENDRAN, Yuvaraj</creator><creator>VANGIPURAPU, Jagadish</creator><creator>PAJUKANTA, Päivi</creator><creator>LUSIS, Aldons J</creator><creator>BONNYCASTLE, Lori L</creator><creator>MORKEN, Mario A</creator><creator>COLLINS, Francis S</creator><creator>MOHLKE, Karen L</creator><creator>BOEHNKE, Michael</creator><creator>ALA-KORPELA, Mika</creator><creator>KUUSISTO, Johanna</creator><creator>LAAKSO, Markku</creator><creator>CEDERBERG, Henna</creator><creator>STANCAKOVA, Alena</creator><creator>PIHLAJAMÄKI, Jussi</creator><creator>SOININEN, Pasi</creator><creator>KANGAS, Antti J</creator><creator>PAANANEN, Jussi</creator><creator>CIVELEK, Mete</creator><creator>SALEEM, Niyas K</creator><general>American Diabetes Association</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8GL</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>5PM</scope></search><sort><creationdate>20131001</creationdate><title>Association of Ketone Body Levels With Hyperglycemia and Type 2 Diabetes in 9,398 Finnish Men</title><author>MAHENDRAN, Yuvaraj ; VANGIPURAPU, Jagadish ; PAJUKANTA, Päivi ; LUSIS, Aldons J ; BONNYCASTLE, Lori L ; MORKEN, Mario A ; COLLINS, Francis S ; MOHLKE, Karen L ; BOEHNKE, Michael ; ALA-KORPELA, Mika ; KUUSISTO, Johanna ; LAAKSO, Markku ; CEDERBERG, Henna ; STANCAKOVA, Alena ; PIHLAJAMÄKI, Jussi ; SOININEN, Pasi ; KANGAS, Antti J ; PAANANEN, Jussi ; CIVELEK, Mete ; SALEEM, Niyas K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c610t-445281d7948c4ef161fca698a0e55812c8841c698bca42bf8ea69de3a7c102b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>3-Hydroxybutyric Acid - blood</topic><topic>Acetoacetates - blood</topic><topic>Area Under Curve</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Blood Glucose - metabolism</topic><topic>Care and treatment</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Diabetes Mellitus, Type 2 - epidemiology</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>European Continental Ancestry Group - genetics</topic><topic>Fasting</topic><topic>Finland - epidemiology</topic><topic>Genetics</topic><topic>Genome-Wide Association Study</topic><topic>Glucose metabolism</topic><topic>Glucose Tolerance Test</topic><topic>Glucose tolerance tests</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Hyperglycemia</topic><topic>Hyperglycemia - blood</topic><topic>Hyperglycemia - epidemiology</topic><topic>Hyperglycemia - genetics</topic><topic>Insulin</topic><topic>Ketone Bodies - blood</topic><topic>Ketones</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Men</topic><topic>Metabolic Syndrome - blood</topic><topic>Metabolic Syndrome - epidemiology</topic><topic>Middle Aged</topic><topic>Organic chemicals</topic><topic>Original Research</topic><topic>Physiological aspects</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Predictive Value of Tests</topic><topic>Risk Factors</topic><topic>Type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MAHENDRAN, Yuvaraj</creatorcontrib><creatorcontrib>VANGIPURAPU, Jagadish</creatorcontrib><creatorcontrib>PAJUKANTA, Päivi</creatorcontrib><creatorcontrib>LUSIS, Aldons J</creatorcontrib><creatorcontrib>BONNYCASTLE, Lori L</creatorcontrib><creatorcontrib>MORKEN, Mario A</creatorcontrib><creatorcontrib>COLLINS, Francis S</creatorcontrib><creatorcontrib>MOHLKE, Karen L</creatorcontrib><creatorcontrib>BOEHNKE, Michael</creatorcontrib><creatorcontrib>ALA-KORPELA, Mika</creatorcontrib><creatorcontrib>KUUSISTO, Johanna</creatorcontrib><creatorcontrib>LAAKSO, Markku</creatorcontrib><creatorcontrib>CEDERBERG, Henna</creatorcontrib><creatorcontrib>STANCAKOVA, Alena</creatorcontrib><creatorcontrib>PIHLAJAMÄKI, Jussi</creatorcontrib><creatorcontrib>SOININEN, Pasi</creatorcontrib><creatorcontrib>KANGAS, Antti J</creatorcontrib><creatorcontrib>PAANANEN, Jussi</creatorcontrib><creatorcontrib>CIVELEK, Mete</creatorcontrib><creatorcontrib>SALEEM, Niyas K</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: High School</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MAHENDRAN, Yuvaraj</au><au>VANGIPURAPU, Jagadish</au><au>PAJUKANTA, Päivi</au><au>LUSIS, Aldons J</au><au>BONNYCASTLE, Lori L</au><au>MORKEN, Mario A</au><au>COLLINS, Francis S</au><au>MOHLKE, Karen L</au><au>BOEHNKE, Michael</au><au>ALA-KORPELA, Mika</au><au>KUUSISTO, Johanna</au><au>LAAKSO, Markku</au><au>CEDERBERG, Henna</au><au>STANCAKOVA, Alena</au><au>PIHLAJAMÄKI, Jussi</au><au>SOININEN, Pasi</au><au>KANGAS, Antti J</au><au>PAANANEN, Jussi</au><au>CIVELEK, Mete</au><au>SALEEM, Niyas K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of Ketone Body Levels With Hyperglycemia and Type 2 Diabetes in 9,398 Finnish Men</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2013-10-01</date><risdate>2013</risdate><volume>62</volume><issue>10</issue><spage>3618</spage><epage>3626</epage><pages>3618-3626</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract>We investigated the association of the levels of ketone bodies (KBs) with hyperglycemia and with 62 genetic risk variants regulating glucose levels or type 2 diabetes in the population-based Metabolic Syndrome in Men (METSIM) study, including 9,398 Finnish men without diabetes or newly diagnosed type 2 diabetes. Increasing fasting and 2-h plasma glucose levels were associated with elevated levels of acetoacetate (AcAc) and β-hydroxybutyrate (BHB). AcAc and BHB predicted an increase in the glucose area under the curve in an oral glucose tolerance test, and AcAc predicted the conversion to type 2 diabetes in a 5-year follow-up of the METSIM cohort. Impaired insulin secretion, but not insulin resistance, explained these findings. Of the 62 single nucleotide polymorphisms associated with the risk of type 2 diabetes or hyperglycemia, the glucose-increasing C allele of GCKR significantly associated with elevated levels of fasting BHB levels. Adipose tissue mRNA expression levels of genes involved in ketolysis were significantly associated with insulin sensitivity (Matsuda index). In conclusion, high levels of KBs predicted subsequent worsening of hyperglycemia, and a common variant of GCKR was significantly associated with BHB levels.</abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>23557707</pmid><doi>10.2337/db12-1363</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Diabetes (New York, N.Y.), 2013-10, Vol.62 (10), p.3618-3626 |
| issn | 0012-1797 1939-327X |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Journals@Ovid Complete |
| subjects | 3-Hydroxybutyric Acid - blood Acetoacetates - blood Area Under Curve Biological and medical sciences Biomarkers - blood Blood Glucose - metabolism Care and treatment Diabetes Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - epidemiology Diabetes Mellitus, Type 2 - genetics Diabetes. Impaired glucose tolerance Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance European Continental Ancestry Group - genetics Fasting Finland - epidemiology Genetics Genome-Wide Association Study Glucose metabolism Glucose Tolerance Test Glucose tolerance tests Health aspects Humans Hyperglycemia Hyperglycemia - blood Hyperglycemia - epidemiology Hyperglycemia - genetics Insulin Ketone Bodies - blood Ketones Male Medical sciences Men Metabolic Syndrome - blood Metabolic Syndrome - epidemiology Middle Aged Organic chemicals Original Research Physiological aspects Polymorphism, Single Nucleotide Predictive Value of Tests Risk Factors Type 2 diabetes |
| title | Association of Ketone Body Levels With Hyperglycemia and Type 2 Diabetes in 9,398 Finnish Men |
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